Five Key Factors That Influence Acidity

I’ve written in schoolmarmish tones before about how pKa is one of the most important measures you can learn in organic chemistry, and not knowing some basic pKa values before an exam is a lot like walking up to a poker table without knowing the values of the hands: you’re going to lose your shirt.

Today we’ll talk about what’s behind the trends in acidity for different molecules and discuss the most important factors that determine these values. Before we get started, however, let’s quickly review the basics of acidity and basicity. Here’s the condensed version:

A conjugate base is what you obtain when you remove a proton (H+) from a compound. For instance, HO(-) is the conjugate base of water. O(2-) is the conjugate base of HO(-). Conversely, conjugate acids are what you obtain when you add a proton to a compound. The conjugate acid of water is H3O(+).

Quick quiz: is pH 1 acidic or basic? pKa is similar to pH in that low (and even negative values) denote strong acids. That’s because pKa is based on the equilibrium:

According to this, anything which stabilizes the conjugate base will increase the acidity. Therefore pKa is also a measure of how stable the conjugate base is. Put another way, strong acids have weak conjugate bases, and vice versa.

With that out of the way, let’s get started.

Factor #1 – Charge.

Removal of a proton, H+ , decreases the formal charge on an atom or molecule by one unit. This is, of course, easiest to do when an atom bears a charge of +1 in the first place, and becomes progressively more difficult as the overall charge becomes negative. The acidity trends reflect this:

Note that once a conjugate base (B-) is negative, a second deprotonation will make the dianion (B 2-). While far from impossible, forming the dianion can be difficult due to the buildup of negative charge and the corresponding electronic repulsions that result.

Factor #2 – The Role of the Atom

This point causes a lot of confusion due to the presence of two seemingly conflicting trends.

Here’s the first point: acidity increases as we go across a row in the periodic table. This makes sense, right? It makes sense that HF is more electronegative than H2O, NH3, and CH4 due to the greater electronegativity of fluorine versus oxygen, nitrogen, and carbon. A fluorine bearing a negative charge is a happy fluorine.

But here’s the seemingly strange thing. HF itself is not a “strong” acid, at least not in the sense that it ionizes completely in water. HF is a weaker acid than HCl, HBr, and HI. What’s going on here?

You could make two arguments for why this is. The first reason has to do with the shorter (and stronger) H-F bond as compared to the larger hydrogen halides. The second has to do with the stability of the conjugate base. The fluoride anion, F(–) is a tiny and vicious little beast, with the smallest ionic radius of any other ion bearing a single negative charge. Its charge is therefore spread over a smaller volume than those of the larger halides, which is energetically unfavorable: for one thing, F(–) begs for solvation, which will lead to a lower entropy term in the ΔG.

Note that this trend also holds for H2O and H2S, with H2S being about 10 million times more acidic.

Factor #3 – Resonance.

A huge stabilizing factor for a conjugate base is if the negative charge can be delocalized through resonance. The classic examples are with phenol (C6H5OH) which is about a million times more acidic than water, and with acetic acid (pKa of ~5).

Watch out though – it isn’t enough for a π system to simply be adjacent to a proton – the electrons of the conjugate base have to be in an orbital which allows for effective overlap (for a dastardly trick question in this vein that routinely stymies Harvard premeds, look here.)

Factor #4 – Inductive effects. Electronegative atoms can draw negative charge toward themselves, which can lead to considerable stabilization of conjugate bases. Check out these examples:

Predictably, this effect is going to be related to two major factors: 1) the electronegativity of the element (the more electronegative, the more acidic) and the distance between the electronegative element and the negative charge.

Factor #5 – Orbitals. Again, the acidity relates nicely to the stability of the conjugate base. And the stability of the conjugate base depends on how well it can accomodate its newfound pair of electrons. In an effect akin to electronegativity, the more s character in the orbital, the closer the electrons will be to the nucleus, and the lower in energy (= stable! ) they will be.

Look at the difference between the pKa of acetylene and alkanes – 25! That’s 10 to the power of 25, as in, “100 times bigger than Avogadro’s number”. Just to give you an idea of scale. That’s the amazing thing about chemistry – the sheer range in the power of different phenomena is awe-inspiring.

There’s actually a mnemonic I’ve found that can help you remember these effects. This is credited to Dr. Christine Pruis, Senior Lecturer at Arizona State University Tempe.

I just wanted to say you are doing an absolutely fantastic job of teaching organic chemistry and making it comprehensible. I’ve been reading your posts for the last few days, and material which was alien to me before as finally started to make sense.

I have a related question. I’ve read that in most cases, resonance stabilization decreases basicity. But is it true that in the cases of guanidines and amidines, resonance increases the basicity? If you could explain how, that’d be great!

I love this site… I hate reading organic chem txt books because most are boooooring but you make studying for O-chem the highlight of my friday evening… You are funny, and your delivery style is absolutely amazing!! I am in O-chem II, barely made it through the first but I am excelling in my second…. Thank you sir for doing this!! I appreciate it more than you know… Good day!

Thank you so much for this summary sheet, I was having so much trouble trying to figure out what made a molecule more acidic – and here it all is! Fully explained and easily understandable. Fantastic stuff.

I just wanted to thank you for all the work you put into this site. I’m an undergraduate at Yale and for the past semester, I’ve been afraid I’ll fail Orgo. Thanks to your site, I no longer feel as stressed because you’ve done such a good job of explaining things. So, yes, thank you!!

I have a problem where I have to determine the most stable conjugate base, which indicates the strongest acid. I just want to know, is it possible to have a strong acid according to its pKa value, but according to atom, resonance, etc. another acid is stronger?

pKa represents an experimental measurement. Experimental measurements are primary – the concepts we pull out of them, such as the factors mentioned, are secondary. So what you’re mentioning isn’t possible, assuming all other variables are the same.

I just don’t seem to understand why does ionic radius increase acidity? I mean, Binding Energy decreases and it’s more easy to lose an electron, if acids are compounds that accept electrons how does acidity increase?

Oh wow, this is amazing. I was starting to think there was no site/book that had exactly this information, this compactly (and brilliantly, might I add) presented. Thank you so much! You’ve got no idea how much this helped (and how much it reduced my study time, god knows we can all do with extra time on our hands :) ). Thanks again!

This is awesome :D ! I never quite got a hold of this topic since the past 2-3 months and now after reading this page it’s all crystal clear to me ! And as for the mnemonic , when i told it to my chem teacher , he was impressed and asked me for the website :D ! Great job, keep it up :D

Organic is my favourite part in chemistry. Your post and contents provided me a good quick revision before my exams and I did extremely well…..
Thanks to you….you have a good way of teaching organic chemistry..
I would definitely recommend this site to my friends who think organic is boaring subject….
Once again thanks…..

Did you get the CARDIO acronym from a Dr. Christine Pruis or Chad’s Reviews from Arizona State University? Dr. Pruis is our Organic Chemistry professor and came up with this acronym 7-8 years ago, so perhaps that is the ‘credit’ you speak of? If so, that is awesome!

When trying to choose a compounds with the highest acidity, according to CARDIO, how do you determine which factor you should prioritize first?
For example:
Suppose you’re trying to determine which compound is more acidic, CHCH or benzene ring?
When you remove the proton the benzene ring is stabilized by resonance but the HCC- has a lot of s character in its orbital. How would you determine which compound is more acidic?

Just wanted to sincerely thankyou for transforming an extremely difficult subject into something comprehensible and futhermore enjoyable. There’s something to be said for that specific talent and it is greatly appreciated. Your use of acronyms and descriptive context have improved both my labs and test marks.
Thank you.

H-bonding makes the solution tightly binded. Like in case of HF (which shows H Bonding) , all the HF molecules are tightly binded to each other so it s not easy for HF to get ionised into H+ and F-( all molecules are already happy in their state of low energy )

Hi James, firstly, a VERY big thank you to you for this amazing website. Its makes organic chemistry SO easy for me to understand!

I think there might be a slight error in the ‘Orbitals’ section of this article. In the graphic, the acidity increases from sp3 to sp (rightward, ascending order) while the signs ( < ) show otherwise. I might be missing something, so please correct me if I am!

Basically the same thing explained in a more elaborate ( slightly better ) way.
Please know that I absolutely love what you’ve done. You’ve made organic chem a million times easier. This is just one of the VERY rare cases where I have found a better reference.

I had a question if you have a moment! I understand the setup of the Ka formula, but for the life of me, I don’t understand what the numbers ARE. When you punch it into the formula, what numbers are you punching in for certain atoms and/or compounds in order to get the Ka, and then get the pKa. It’s not explained in my text, or any resources I may have. My professor is also not very great at translating our questions in class.

I have been looking for a thorough explanation like this for such a long time, being unable to find one. This is really helpful for a med student struggling with his Chem & Intro to Bio exam, thank you so much James.

Hi I had a question. When taking inductive effects (electron withdrawin and electrons donating) into account are we looking at the conjugate base or the acid itself if we wanted to apply rules such as neutral N or O are considered electrons donors?

You’re looking at how well the stabilize (or destabilize) the conjugate base. Anything which stabilizes the conjugate base will result in a stronger acid (and vice versa). For example HOCF3 is a stronger acid then HOCH3 because those three fluorine atoms help to stabilize the conjugate base, -OCF3 through the inductive effect.

I love your site and it has helped me a lot :) just one doubt, is electronegativity of an atom related to it’s tendency to act as a LEWIS base. For example NH3 , and PH3,
we know that NH3 is stronger but why doesn’t the electronegativity of the central atom come under consideration here? N has a high electronegativity so it’s tendency to donate lone pair of electrons should be low right? Please please please help.

You mention two factors, electronegativity and size. From first principles it’s difficult to anticipate exactly which would be most important. However, from running experiments on reaction rates (and measuring the results) PH3 tends to be a better Lewis base (“Nucleophile”) than NH3 . The explanation is, the lone pair on phosphorus is less tightly held than that on nitrogen, so it is more “easily” donated. [This is NOT a dumb question – the issue is somewhat complex and can depend on the type of electrophile. I haven’t gotten into Hard and Soft acids and bases but I suggest you look it up]

May God bless you sir .
My sister had her exams and needed help.
I, although being a student of commerce stream , decided that I had to help her in every way I could. But I knew I sucked at organic chemistry in school,and so did my little sister .
I found your site , and the next day I am understanding things better than I ever did , .. …I would look up about anything I didn’t know on your website .
getting to the main thing , my sister scored 97 in chemistry , full marks in the organic portion.
Thank you sir :’-).

I am having difficulty determining the relative acidity of amines and ammonium ions. For instance:
a) H3C-NH3+
b) H2C=NH2+
c) HCNH+
d) (CH3)3NH+
How does the difference in bonding between carbon and nitrogen effect the acidity?

Your article has been very helpful and I now have actually a chance to pass my exams in general chemistry! I just want to ask, we have to apply these factors in sequence, as you have given them or not??? I mean first the charge, after the atom etc??

All was awesome but I just confused in inductive effect when u compares acidities of halogen acid? As electronegative difference between F and O is less as compared to OH ? So how H lose? May be my question is low of standard as I m new kindly help

About Master Organic Chemistry

After doing a PhD in organic synthesis at McGill and a postdoc at MIT, I applied for faculty positions at universities and it didn’t work out, yada yada yada. So I decided to teach organic chemistry anyway! Master Organic Chemistry is the resource I wish I had when I was learning the subject.